Peptides vaginal delivery

Conventional systems do not offer sufficient flexibility in controlling drug-release rate and sustaining the release over time periods extending from days to months. Therefore specific modified release vaginal delivery systems are continuously under development and are based on mucoadhesive systems. Penetration enhancement may represent a necessary feature for certain delivery systems, particularly when the absorption regards a macromolecule (such as a peptide or a protein). 

Different drug delivery systems have been proposed for vaginal delivery of peptides and proteins. The first one was a mucoadhesive gel based on polyacrylic acid intended for vaginal administration of insulin [96]. More recently, microparticulate systems such as starch and hyaluronan ester (HYAFF) microspheres have been proposed for vaginal delivery of insulin... 

No matter what degree of optimization can actually be achieved via this route, it must be remembered that vaginal delivery is only applicable to approximately 50% of the population. Thus it may be that the true potential of this route lies in the treatment of female-specific conditions, such as in the treatment of climacteric symptoms of the menopause etc., rather than more general applications such as insulin/peptide delivery. 

Proteins and peptides, particularly in the presence of absorption enhancers, can be successfully administered by this route, although surfactant-based enhancers are apparently not effective in the vagina. Vaginal enzymes, especially the proteases, are likely to present problems in the vaginal delivery of proteins and peptides. 

Introduction Oral Delivery of Proteins and Peptides Buccal Delivery Vaginal Delivery of Insulin Transdermal Delivery Rectal Delivery of Protein Drugs... 

A host of bioadhesive controlled release systems have been proposed in recent years. Among the most commonly studied applications of bioadhesive materials is the area of buccal controlled delivery [408], The buccal delivery of small peptides from bioadhesive polymers was studied by Bodde and coworkers [409], and a wide range of compositions based on poly(butyl acrylate) and/or poly(acrylic acid) gave satisfactory performance. Bioadhesive poly(acrylic add)-based formulations have also been used for oral applications [402,410] for the sustained delivery of chlorothiazide [410] and for a thin bioadhesive patch for treatment of gingivitis and periodontal disease [411]. Other bioadhesive applications of polyelectrolytes include materials for ophthalmic vehicles [412,413], and systems for oral [410,414,415-419], rectal [420,421] vaginal [422] and nasal [423] drug delivery. 

Richardson, J.L., and L. Ilium. 1992. Routes of delivery—Case studies. The vaginal route of peptide and protein drug delivery. Adv Drug Deliv Rev 8 341. 

Different microsphere formulations have been proposed for the delivery of peptides and protein via vaginal mucosa. This will be considered in Section 22.8. 

In recent years, efforts have been made to find methods to increase peptide and protein absorption via the vaginal mucosa by the use of penetration enhancers, enzyme inhibitors, and bioadhesive drug delivery systems. 

Due to the lack of activity after oral administration for most peptides and proteins, administration by injection or infusion - that is, by intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration - is frequently the preferred route of delivery for these drug products. In addition, other non-oral administration pathways have been utilized, including nasal, buccal, rectal, vaginal, transder-mal, ocular, or pulmonary drug delivery. Some of these delivery pathways will be discussed in the following sections in the order of the increasing biopharmaceutic challenges to obtain adequate systemic exposure. 

Peptide delivery It has also been reported that a polycarbophil hydrogel formulation increased the vaginal membrane permeability of GnRH, in comparison to a solution, in rats. Co-administration of the GnRH loaded gel with various enzyme inhibitors (EDTA, sodium taurodihydrofusidate and sodium laurate) resulted in ovulation-inducing activity comparable with that of a sc injection. 

Hafez E.S.E. and Evans T.N. (eds) (1978) The Human Vagina. Elsevier/North-Holland Biomedical Press, Amsterdam. Okada, H. (1991) Vaginal route of peptide and protein drug delivery. In Peptide and Protein Drug Delivery (V.H.L. Lee, ed.). Marcel Dekker, New York, pp. 633-666. 

Muranishi, S., Yamamoto, A. and Okada, H. (1993) Rectal and vaginal absorption of peptides and proteins. In Biological Barriers to Protein Delivery. (Audus K.L. and Raub T.J., eds). Plenum Press, New York, pp. 199-227. Zhou, X.H. (1994) Overcoming enzymatic and absorption barrier to non-parenterally administered protein and peptide drug. J. Contr. Rel 29 239-252. 

Microparticles and nanoparticles present some advantageous features, namely mucoadhesive properties. They have demonstrated some potential in vaginal drug delivery, particularly in the formulation of delivery systems for vaccines or peptides and proteins [160, 161], Nonetheless, these particles have to be incorporated in adequate carrier systems in order to be delivered. This task has been shown to be complex, it being hard to achieve controlled-release and steady-release profiles. 

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